十一、研究計畫中英文摘要：請就本計畫要點作一概述，並依本計畫性質自訂 關鍵詞。
（二）計畫英文摘要。（五百字以內）
Angiogenesis is required to sustain primary tumor enlargement as well as metastasis. The induction of tumor angiogenesis is mediated by the increased production of various angiogenic molecules released by tumor cells, including vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs) and cytokine. Among the angiogenic factors, VEGF was found to be the most potent. The expression of VEGF has been shown to be markedly associated with the secration of cytokine, such as interleukin,(IL)-12, interferon (IFN) and tumor necrosis factor (TNF)-α by the immune system.
Epidemiologic studies have shown that high lycopene intakes are associated with low risk of several types of cancer. Lycopene is known to possess antioxidant, immunomodulatory and anticancer activities, especially prostate cancer, and is an important topic of anticancer research. It should be noted that the
immuno-regulatory action is realted with anti-angiogenesis. However, it is unclear whether lycopene can inhibit angiogenesis via immunomodulatory action.
We have identified several important issues in review of the literature. We intend to study two major issues that we are able to tackle and resolve. One issue is
whether lycopene can inhibit angiogenesis and how they exert these effects. We recently showed that lycopenemediated angiogenic factors, including the inhbition of VEGF and MMPs and and up-regulation of IL-12 secretion in nude mice (Huang et al., J. Nutr. 2008). However, the anti-angiogenic effects and mechanisms of action of lycopene have not been reported. Another isuue is the possible mechanism about immunomodulation. To examine the following issues, we intend to use the human umbilical vein endothelial cell lines (HUVEC) as in vitro angiogenesis model.
1) In the first year, we will evaluate the immunomodulatory effects of lycopene by analyzing the production of cytokines in mononuclear cells stimulated with lycopene in order to provide insights into the immune function that controls angiogenesis in response to lycopene.
2) In the second year, we will investigate the anti-angiogenic effect of lycopene in an ex-vivo model, closely mimicking physiological conditions. Gerbils will be
supplemented with lycopene orally, and their serum used in in vitro studies on angiogenesis of HUVEC, and the imunemodulatory mechanism.
3) In the third year, we will investigate the in in ex-vivo and in vivo anti-angiogenic effects of lycopene and the mechanisms.
This research project is expected to increase our knowledge of the
anti-angiogenic effects and immunomodulatory mechanism of lycopene. In addition,
these studies can not only promote the level of basic research in Taiwan, but also contributes directly or indirectly to the health of people worldwide.
Keywords: lycopene, immunomodulation, anti-angiogenesis, cytokine
